The PET Radiochemistry Laboratory of NIBIB has had a productive year of research. The majority of our effort has focused on projects that are collaborations with other NIH investigators. [unreadable] [unreadable] We have continued to expand our project on the imaging of HER2 receptor in certain tumors with an extensive small animal PET imaging program using a human breast cancer xenograft model in athymic nude mice. This is a collaborative project among the NIBIB PET Radiochemistry Laboratory, the group of Jacek Capala in NCI's Radiation Oncology Branch, and Affibody AG (CRADA partner of Dr. Capala). We have optimized a manual radiosynthetic procedure for preparing an F-18 radiolabeled maleimide that will couple selectively with the lone cysteine residue in the HER2 specific Affibody. Adaptation of a commercial radiochemical synthesis apparatus to this radiosynthesis is in progress. The first biological study which involved the use of our small animal PET imaging system, is included in the bibliography of this report. A second study that demonstrates the utility of this Affibody tracer to evaluate the effects of tumor therapy and receptor modulation on tracer uptake has been submitted for publication.[unreadable] [unreadable] We have a collaborative project with the NIAID on the development of an F-18 radiolabeled nucleoside analog reverse transcriptase inhibitor (FPMPA--1-(6-amino-9H-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid). The goal is to be able to study the biodistribution of the analogous non-fluorine containing drug, tenofovir, as a function of chronic treatment. The radiochemical synthesis has been published. We have demonstrated that the biodistribution of our F-18 analogue is very similar to the non-fluorine containing parent compound is all tissues except kidney and lung. We have also conducted biodistribution studies with PET imaging. Uptake of the tracer is highest in the kidney in normal rats.[unreadable] [unreadable] In collaboration with Kenneth Jacobson, NIDDK senior investigator, we have evaulated two bromine-76 radiolabeled compounds, which target the adenosine A3 receptor, as potential tracers for inflammation processes (neuroinflammation, tumor infiltration, etc). The chemical synthesis of an agonist and an antagonist ligand , both with high affinity, had previously been conducted in Dr. Jacobson's laboratory. The appropriate tin precursors for radiobromination were prepared and successfully radiobrominated. The validation of these tracers has proved difficult due to the low concentration of these receptors in normal rats. The only tissue with a reasonable concentration of A3 receptors is the testes. However, this tissue is somewhat protected by a testes-blood barrier. We have some indication that the antagonist ligand my show specific testes uptake, however, more support will be needed from tumor or inflammation models.[unreadable] [unreadable] Last year, in collaboration with Dr. Kenner Rice, NIDA senior investigator, we prepared corticotropin releasing hormone ligands labeled with Br-76. We discovered some interesting chemistry and have drafted a manuscript that will be submitted this year. In addition the biological properties of these compounds have been studied using in vivo biodistribution measurements and the data is currently being evaluated for manuscript preparation.[unreadable] [unreadable] We are expanding our repertoire of available radionuclides with investigations of the metallic positron emitting radionuclide Cu-64. With its 12 h half-life, we believe this radionuclide may allow application of PET to the some larger proteins that exhibit relatively slow kinetics. In addition, the nuclear decay properties of this radionuclide may be used therapeutically. [unreadable] [unreadable] [unreadable] Our training component was very successful. A post-doctoral fellow began on April 2. We have a new post-baccalaureate IRTA who began in July. We had one summer student this year.